Immunohistochemical Analysis of HER2, EGFR, and Nectin-4 Expression in Upper Urinary Tract Urothelial Carcinoma

• Published in: Anticancer research 2023-01, Vol.43 (1), p.167-174
• Main Authors: Hashimoto, Mamoru, Fujita, Kazutoshi, Tomiyama, Eisuke, Fujimoto, Saizo, Adomi, Shogo, Banno, Eri, Minami, Takafumi, Takao, Tetsuya, Nozawa, Masahiro, Fushimi, Hiroaki, Yoshimura, Kazuhiro, Nonomura, Norio, Uemura, Hirotsugu
• Format: Article
• Language: English
• Subjects: Bladder cancer; Cancer; Carcinoma, Transitional Cell - genetics; Carcinoma, Transitional Cell - metabolism; Chemical analysis; Epidermal growth factor; Epidermal growth factor receptors; ErbB protein; ErbB Receptors - genetics; ErbB Receptors - metabolism; ErbB-2 protein; Growth factors; Humans; Nectin; Nectins - genetics; Nectins - metabolism; Prognosis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Receptors; Retrospective Studies; Survival; Therapeutic targets; Ureteral Neoplasms - genetics; Ureteral Neoplasms - metabolism; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary tract; Urinary Tract - pathology; Urogenital system; Urothelial carcinoma
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.16146

Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, often discovered at an advanced stage at diagnosis. Nectin-4 is expressed in a broad range of patients with UTUC and is associated with poor progression-free survival. The receptors of the erythroblastosis oncogene B (ErbB) family are potential therapeutic targets for urothelial carcinoma. Herein, we aimed to investigate the relationship of nectin-4 and ErbB family receptors, namely epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in patients with UTUC. Targeted therapies for these receptors could be used in sequence or in combination for increasing treatment efficiency. We performed immunohisto-chemical analysis for HER2, EGFR, and nectin-4 using tissue microarrays. A total of 98 UTUC patients were included in the study. We investigated the impact of EGFR and HER2 expression status on recurrence-free survival (RFS) and cancer-specific survival (CSS) of all patients. The percentages of patients positive for HER2, EGFR, and nectin-4 were 97%, 70%, and 65%, respectively. The co-expression rates of HER2-EGFR, HER2-nectin-4, and EGFR-nectin-4 were 69%, 64%, and 47%, respectively. The number of patients positive for all three receptors was 47%. Higher HER2 levels were significantly associated with worse CSS and RFS. Higher EGFR levels were associated with a worse CSS. HER2, EGFR, and nectin-4 were highly expressed in UTUC. Combination of HER2-, EGFR-, and nectin-4-targeted therapy may be an effective option for the treatment of patients with UTUC.